Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
Muscular dystrophy (MD) is the name given to a group of genetic disorders characterized by progressive muscle weakness and wasting.1 There are many types of muscular dystrophies based on the causative genetic mutation. Each type of disease has its own clinical features and symptoms. Some of the common features of many types of muscular dystrophy are muscle pain, difficulty walking or running, waddling gait, scoliosis, swallowing and breathing problems, and heart complications.2
A diagnosis of muscular dystrophy can be reached on the basis of phenotype following a physical exam and family history of the patient. There are also several tests available to help diagnose muscular dystrophies. These include blood tests to assess the levels of creatine kinase and other enzymes in the serum, electromyography, magnetic resonance imaging (MRI), muscle biopsy, and genetic testing.
Physical Exam and Family History
A patient presenting with muscle weakness may have pseudohypertrophy, lumbar spine deviation, gait abnormalities, and reduced muscle reflexes, which can be evident during a physical examination.3 The gracilis, semimembranosus, semitendinosus, and sartorius muscles may be affected. Other features that may be evident during a physical exam are equinovarus foot deformities, a tilted pelvis, and contracture.4
Since MD is a genetic condition, patients usually have other family members who are also affected by muscle weakness. However, because there are many different types of muscular dystrophies each with a different causative genetic mutation, the inheritance pattern, age of symptom onset, and rate of progression can vary greatly. Taking a careful family history can be the first step in identifying the inheritance pattern of the disease in question.
Serum Creatine Kinase Levels
Creatine kinase (CK) is highly expressed in muscle cells and converts ATP into ADP, playing a major role in energy metabolism. When muscle tissue gets damaged CK leaks into the bloodstream. So, high levels of CK in serum can be indicative of muscular dystrophy but also myocardial infarction, rhabdomyolysis due to strenuous exercise or injury, autoimmune myositides, and acute kidney injury.5
CK levels are at their highest during the active phase of the disease. However, as the disease progresses and muscle mass is gradually lost, levels of serum CK tend to decrease.4
Serum CK levels cannot determine the type of muscular dystrophy that a patient has but research has shown that measuring levels of different enzyme profiles including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactic dehydrogenase (LDH) may help identify different types of muscular dystrophy and guide the choice of genetic analysis that should be conducted.6
Electromyography can be useful in differentiating muscular dystrophy from other causes of muscle weakness such as motor neuron disease by measuring the electrical impulse along nerves, nerve roots, and muscle tissue.
The study of one proximal and one distal muscle from one upper extremity and one lower extremity and the thoracic paraspinals is recommended. Muscles that are commonly assessed are the deltoid, biceps, triceps, pronator teres, extensor digitorum communis, first dorsal interosseous, gluteal muscles, iliopsoas, vasti, tibialis anterior, and gastrocnemius.7
Electromyography can also help identify the muscles to be biopsied for further diagnostic testing.
MRI can detect patterns of muscle involvement in different types of muscular dystrophies and differentiate between various forms of the disease.
For example, muscles involved in Duchenne muscular dystrophy (DMD) include gastrocnemii, gluteus maximus, and adductor magnus, and then the quadriceps, rectus femoris, and biceps femoris as the disease progresses.8
In facioscapulohumeral dystrophy, upper girdle muscles that are most frequently affected in an asymmetric fashion include the trapezius, teres major, and serratus anterior.
Finally, some forms of limb-girdle muscular dystrophy are characterized by a predominant fatty degeneration of the gluteus minimus muscle and the posterior segments of the thigh and calf muscles.
Muscle biopsy plays a key role in diagnosing MD. Biopsied samples can show 2 types of histopathological abnormalities: neurogenic atrophy and myopathic changes.9
The sample can also be stained immunohistochemically or analyzed under an electron microscope to increase the diagnostic yield. It can show disease-specific changes and can help clinicians identify the type of muscular dystrophy a patient may have.
Because there is such a wide range of muscular dystrophies caused by different genetic mutations, it can be hard to decide which gene to test in order to reach a final diagnosis.
However, the results of other tests such as electromyography, MRI, and muscle biopsy may give an indication about the type of muscular dystrophy the patient may have and guide the genetic diagnostic process.
- Overview – Muscular dystrophy. NHS. May 24, 2018. Accessed May 19, 2021.
- Muscular dystrophy. Cleveland Clinic. June 22, 2020. Accessed May 19, 2021.
- Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. Accessed May 19, 2021.
- LaPelusa A, Kentris M. Muscular dystrophy. StatPearls. November 20, 2020. Accessed May 19, 2021.
- Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. Published online January 11, 2012. doi:10.1155/2012/960363
- Zhu Y, Zhang H, Sun Y, et al. Serum enzyme profiles differentiate five types of muscular dystrophy. Dis Markers. Published online April 29, 2015. doi:10.1155/2015/543282
- Paganoni S, Amato A. Electrodiagnostic evaluation of myopathies. Phys Med Rehabil Clin N Am. 2013; 24(1):193–207. doi:10.1016/j.pmr.2012.08.017
- Politano L, Nigro G. Magnetic resonance imaging in muscular dystrophies. Acta Myol. 2015; 34(2-3):93–94.
- Joyce NC, Oskarsson B, Jin LW. Muscle Biopsy Evaluation in Neuromuscular Disorders. Phys Med Rehabil Clin N Am. 2012; 23(3):609–631. doi:10.1016/j.pmr.2012.06.006
Article reviewed by Debjyoti Talukdar, MD, on July 1, 2021.